Molecules for the photodynamic treatment of tumors and hyperplasias
This invention relates to pharmaceutical compositions comprising a sulfonated biological precursor of thymidine, such as a precursor of 4-thiothymidine (4-TT), and their use in the photodynamic treatment of skin hyperplasias, including cancer, psoriasis, actinic keratosis and keloids, by topical or systemic administration.
1. A method for treating a patient suffering from skin and internal epithelia hyperplasias comprising administering a pharmaceutical composition comprising a sulfonated de novo synthesis precursor of thiothymidine and a carrier, wherein the sulfonated de novo synthesis precursor of thiothymidine is a precursor of 4-thiothymidine, to a patient in need thereof, in a topical or systemic manner, and subsequently exposing the hyperplasia to UV-A irradiation.
2. The method according to claim 1 , wherein the UV-A irradiation has a wavelength comprising the absorption peak of the sulfonated de novo synthesis precursor of 4-thiothymidine and is comprised between 300 and 600 nm.
3. The method according to claim 1 , wherein the UV-A irradiation is repeated several times in the period following a single application of the composition.
4. The method according to claim 1 , whereby cellular death is caused by apoptosis or necrosis.
5. The method according to claim 1 , wherein the hyperplasia is selected from the group consisting, of skin, head and neck, stomach, lung, colon and bladder cancer, psoriasis, actinic keratosis and keloids.
6. The method according to claim 1 , wherein the sulfonated de novo synthesis precursor of 4-thiothymidine is selected from the group consisting of 4-thioorotate, 4-thiodihydroorotate, 4-thiomidylate, and carbamoyl-thioaspartate.
7. The method according to claim 6 , wherein the sulfonated de novo synthesis precursor of 4-thiothymidine is further derivatized at the 6 carboxylic position into an ester by reaction with an alcohol.
8. The method according to claim 7 , where the composition further contains a penetration enhancer.
9. The method according to claim 8 , wherein the penetration enhancer is a sulfoxide.
10. The method according to claim 9 , wherein the sulfoxide is selected from the group consisting of dimethylsulfoxide, decylmethylsulfoxide and dimethylsulfoacetamide.
11. The method according to claim 8 , wherein the penetration enhancer is a hydroxylated polymer.
12. The method according to claim 11 , wherein the hydroxylated polymer is polyethylene glycol or polypropylene glycol.
13. The method according to claim 8 , wherein the penetration enhancer is a natural microfibrillated polysaccharide.
14. The method according to claim 13 , wherein the natural microfibrillated polysaccharide is selected from the group consisting of microfibrillated cellulose, microfibrillated starch, microfibrillated dextran and cyclodextrins.